The field of the invention is treatment to reduce or prevent smooth muscle contraction, especially with respect to the musculature of an organ such as a uterus or a urinary bladder.
In certain situations, notably premature labor, the uterine musculature is triggered by various stimuli to contract at a time when it is undesirable or even life-threatening to do so. If the fetus is near term but has not yet produced the surfactant that will enable it to breathe properly after birth, quieting uterine contractions and thereby delaying delivery for a few days may be sufficient: during those few days, the mother is treated with cortisol to induce immediate surfactant production by the fetus, which can then be delivered without the threat of developing the often-fatal condition known as hyaline membrane disease. In other cases, labor may begin so early in gestation that it must be controlled for weeks or even months to permit the fetus to mature in utero adequately to survive outside the womb. Present methods of preventing uterine contractions in cases of premature labor or other circumstances in which delay of delivery is desirable include mechanical suturing of the cervix (circlage) in early pregnancy, bed rest, and/or intravenous treatment with a tocolytic agent such as a .beta..sub.2 adrenergic agonist (e.g., ritodrine, terbutaline, metaproterenol, albuterol or fenoterol); magnesium sulfate; ethanol; a calcium channel antagonist (e.g., nifedipine); or an inhibitor of prostaglandin synthesis (e.g., indomethacin). [Goodman and Gilman's The Pharmacological Basis of Therapeutics (7th Ed.) Gilman et al., ed.; Macmillan Publishing Co., N.Y., 1985, pages 942-943.] In addition, the use of intravenous nitroglycerin (an NO donor compound) has been reported to relax a postpartum uterus (Altabef et al., Am. J. Obstet. Gynecol. 166:1237-1238, 1992). Such drugs, however, have certain systemic side effects that may be unpleasant or harmful to the mother, and possibly to the fetus.
In an analogous manner, the often painful constrictions of urinary bladder musculature associated with the presence of an indwelling urinary catheter are typically relieved with intravenous smooth muscle relaxants that frequently cause undesired systemic effects (Resnick and Yalla, Chapter 14 in Campbell's Urology, 6th Ed., W. B. Saunders Co., 1992, pages 652-655).